The present invention, in some embodiments thereof, relates to material science and, more particularly, but not exclusively, to doped metal oxide nanoparticles, processes of preparing same, surface coatings containing same and uses thereof in, for example, reducing or preventing growth of microorganisms.
Despite being successful in controlling or eliminating bacterial infections, widespread use of antibiotics both in human medicine and as a feed supplement in poultry and livestock production has led to drug resistance in many pathogenic bacteria (McCormick J. B., Curr Opin Microbiol 1:125-129, 1998). The evolution and spread of resistance genetic determinants, multidrug resistant (MDR) bacteria that cause life-threatening infections have been increasingly emerged (A. P. Magiorakos et al. Clin. Microbiol. Infect. 2012, 18, 268), and as such, the effectiveness of antibiotics has greatly diminished in the last decade. Furthermore, as resistance spreads among bacteria, there is great concern that antibiotics treatment will become increasingly less effective and, in some cases, completely ineffective.
Hospital-acquired (nosocomial) infections caused by antibiotic-resistant bacteria result in patient suffer and mortality and impose a substantial burden on the medical system due to extended periods of hospitalization. The economic impact of managing infections caused by nosocomial infections is substantial, and current costs are estimated to be more than $4 billion annually [Harrison and Lederberg (ed.), Antimicrobial resistance: issues and options. National Academy Press, Washington, D.C. pp. 1-7, 1998].
Bacterial attachment to surfaces leading to the formation of communities of bacterial cells is a major problem in many diverse settings. This sessile community of microorganisms, also termed a biofilm, is attached to an interface, or to each other, and embedded in an exopolymeric matrix. It manifests an altered growth rate and transcribes genes that free-living microorganisms do not transcribe. The most characteristic phenotype of the biofilm mode of growth is its inherent resistance to disinfection, antimicrobial treatment and immune response killing.
Medical implants and in-dwelling devices are especially prone to bacterial colonization and biofilm formation, and removal of the infected device is required in such cases due to the ineffectiveness of conventional antibiotic therapy against device-associated biofilm organisms. It has been estimated that the number of implant-associated infections approaches 1 million/year in the US alone, and their direct medical costs exceed $3 billion annually (R. O. Darouiche, Preventing infection in surgical implants, US Surgery, 2007, 40).
The inherent resistance of biofilms to killing and their pervasive involvement in implant-related infections has prompted research in the area of biocidal surfaces/coatings. Such anti-biofilm coatings may also be in use for various industrial applications such as drinking water distribution systems and food packaging.
Another class of difficult to eradicate microorganisms includes fungi. The number of antifungal agents is limited and most are non-specific as to the organism affected and can be detrimental to the environment, inducing toxicity to plant and animals. Inorganic metal oxides such as ZnO, MgO, and CuO are being increasingly used in antimicrobial applications. The key advantages of using inorganic oxides compared to organic antimicrobial agents are their stability, robustness, and long shelf-life.
Research in the area of nanometric metal oxides in general, and nanometric ZnO, MgO, and CuO in particular, has demonstrated a clear size dependence of various properties, such as, for example, electromagnetic, optical, and catalytic properties, as well as antibacterial activities (P. Madahi et al. Phys. Scr. 2011, 84; G. Applerot et al. Adv. Funct. Mater. 2009, 19, 842; G. Applerot et al. Small 2012, 8, 3326).
Oxygen is essential for most living organisms, but is also a precursor of reactive oxygen species (ROS), which can damage cellular components such as proteins, lipids and nucleic acids. ROS include oxygen-containing ions (e.g., superoxide; •O2−), small molecules that contain peroxide (e.g., hydrogen peroxide; H2O2), free radicals (e.g., hydroxyls; •OH) and singlet oxygen (Droge et al. Physiol. Rev. 2002, 82:47-95; Lee et al. Aust. J. Chem. 2011, 64, 604).
During interaction with water, some metal oxides produce ROS that are known to kill bacteria (J. Sawai, et al. J. Chem. Eng. Jpn. 1996, 29, 627). The creation of ROS by metal oxides depends on the presence of defect sites in the structure of the metal oxide nanoparticles.
The rapid development of different methods for the fabrication and deposition of nanomaterials on polymer and glass surfaces significantly enhanced their application in electronic devices and biotechnology. Recently, some low temperature methods for the deposition nanoparticles on a glass substrate, such as, for example, electrode plating of spin-coated nanoparticles and deposition of nanoparticles on modified glass slides, were reported (K. H. Lee et al. Langmuir, 2007, 23, 1435).
Sonochemistry is concerned with the effect of ultrasonic irradiation on chemical systems. The chemical effects of ultrasonic irradiation arise from acoustic cavitation, namely, the formation, growth, and implosive collapse of bubbles in a liquid medium. The compression of the bubbles during cavitation is more rapid than the thermal transport, which generates short-lived, localized hotspot bubbles reaching temperatures as high as 5000 K, pressures of roughly 1000 Atm, and heating and cooling rates above 1×1010 K/s (A. Gedanken, Ultrason. Sonochem., 2004, 11 (2)).
Ultrasonic irradiation has been proven as an effective technique for the synthesis of nanomaterials (R. Gottesman, et al. Langmuir 2011, 27(2), 720). This technique further enables controlling the particle size of the product by varying the concentration of the precursors in the solution.
Ultrasonic irradiation has been proven as being effective for the deposition of nanoparticles on polymeric matrices since the high-velocity fluid agitation, shock waves and energetic jets that are created during the compression of the bubbles near a solid substrate, propel the newly-formed nanoparticles at the solid substrate at a very high speed (>100 m/s), which has been shown as being sufficient to embed the particles in the substrate (Y. Didenko and K. S. Suslick, Nature, 2002, 418, 394).
Utilizing sonochemistry as a coating route further enables combining the synthesis of various nanomaterials and their deposition on various substrates in a single operation without the aid of a binder. Previous works demonstrated the use of sonochemistry as a perspective method for coating various substrates such as paper (K. Ghule et al. Green Chem., 2006, 8, 1034), glass surfaces (G. Applerot et al. Appl. Surf. Sci., 2009, 256S, S3) and fabrics (I. Perelshtein et al. ACS Appl. Mater. Interfaces, 2009, 1 (2), 361) with ZnO nanoparticles.
U.S. patent application having Publication No. 2011/0097957 teaches a system for preparing antimicrobial fabrics, coated sonochemically with metal oxide nanoparticles to thereby form uniform deposition of the metal oxide.
P Madahi et al. [Phys. Scr. 2011, 84] teach that doping of ZnO with Mg or Sb leads to only a slight increase in the antibacterial activity of nanosized ZnO.
Prabhakaran et al. [J. Cryst. Growth 2003, 250, 77] teach the synthesis of a Zn-doped CuO composite and characterize it by chemo-physical properties such as its crystalline structure and magnetization as a function of temperature.
Huan-Ming et al. [Angewandte Chemie International Edition 2009, 48, 15, 2727] teach sonochemical synthesis of ZnO nanoparticles Doped with Mg. The Mg-doped ZnO nanoparticles exhibit bright, stable photoluminescence both in colloidal dispersions and in the solid state and are formed by doping Mg ions into ZnO nanoparticles by sonochemical synthesis. The preparation of Mg-doped ZnO is performed by applying sonication procedure on already synthesized ZnO nanoparticles in the presence of magnesium acetate.
Vidic et al. [J. Nanopart. Res. (2013) 15, 1595] teach the synthesis and physicochemical characterization of phase separated nanostructured of Zn-doped MgO, whose antibacterial activity was compared to its pure ZnO and MgO nanoparticles.
WO 2011/033040 teaches a method of preparing ZnO nanoparticles doped with Cu or Mg. WO 2011/033040 teaches that Cu-doped or Mg-doped ZnO nanoparticles have a higher antibacterial activity than ZnO nanoparticles.